Development and Comparison of Time Series Models in Predicting Severe Fever with Thrombocytopenia Syndrome Cases - Hubei Province, China, 2013-2020.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus, which has a high mortality rate. Predicting the number of SFTS cases is essential for early outbreak warning and can offer valuable insights for establishing prevention and control measures. Methods: In this study, data on monthly SFTS cases in Hubei Province, China, from 2013 to 2020 were collected. Various time series models based on seasonal auto-regressive integrated moving average (SARIMA), Prophet, eXtreme Gradient Boosting (XGBoost), and long short-term memory (LSTM) were developed using these historical data to predict SFTS cases. The established models were evaluated and compared using mean absolute error (MAE) and root mean squared error (RMSE). Results: Four models were developed and performed well in predicting the trend of SFTS cases. The XGBoost model outperformed the others, yielding the closest fit to the actual case numbers and exhibiting the smallest MAE (2.54) and RMSE (2.89) in capturing the seasonal trend and predicting the monthly number of SFTS cases in Hubei Province. Conclusion: The developed XGBoost model represents a promising and valuable tool for SFTS prediction and early warning in Hubei Province, China.

Potential novel Colpodella spp. (phylum Apicomplexa) and high prevalence of Colpodella spp. in goat-attached Haemaphysalis longicornis ticks in Shandong province, China.

Tick-borne Apicomplexan parasites pose a significant threat to both public health and animal husbandry. Identifying potential pathogenic parasites and gathering their epidemiological data are essential for prospectively preventing and controlling infections. In the present study, genomic DNA of ticks collected from two goat flocks (Goatflock1 and Goatflock2) and one dog group (Doggroup) were extracted and the 18S rRNA gene of Babesia/Theileria/Colpodella spp. was amplified by PCR and sequenced. Phylogenetic analysis was conducted based on the obtained sequences. The differences in pathogen positive rates between ticks of different groups were statistically analyzed using the Chi-square or continuity-adjusted Chi-square test. As a result, two pathogenic Theileria (T.) luwenshuni genotypes, one novel pathogenic Colpodella sp. HLJ genotype, and two potential novel Colpodella spp. (referred to as Colpodella sp. struthionis and Colpodella sp. yiyuansis in this study) were identified in the Haemaphysalis (H.) longicornis ticks. Ticks of Goatflock2 had a significantly higher positive rate of Colpodella spp. than those from Goatflock1 (χ2=92.10; P = 8.2 × 10-22) and Doggroup (χ2=42.34; P = 7.7 × 10-11), and a significantly higher positive rate of T. luwenshuni than Doggroup (χ2=5.38; P = 0.02). However, the positive rates of T. luwenshuni between Goatflock1 and Goatflock2 were not significantly different (χ2=2.02; P = 0.16), and so as the positive rates of both pathogens between Goatflock1 and Doggroup groups (P > 0.05). For either Colpodella spp. or T. luwenshuni, no significant difference was found in prevalence between male and female ticks. These findings underscore the potential importance of Colpodella spp. in domestic animal-attached ticks, as our study revealed two novel Colpodella spp. and identified Colpodella spp. in H. longicornis for the first time. The study also sheds light on goats' potential roles in the transmission of Colpodella spp. to ticks and provides crucial epidemiological data of pathogenic Theileria and Colpodella. These data may help physicians, veterinarians, and public health officers prepare suitable detection and treatment methods and develop prevention and control strategies.

Time series models in prediction of severe fever with thrombocytopenia syndrome cases in Shandong province, China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV). Predicting the incidence of this disease in advance is crucial for policymakers to develop prevention and control strategies. In this study, we utilized historical incidence data of SFTS (2013-2020) in Shandong Province, China to establish three univariate prediction models based on two time-series forecasting algorithms Autoregressive Integrated Moving Average (ARIMA) and Prophet, as well as a special type of recurrent neural network Long Short-Term Memory (LSTM) algorithm. We then evaluated and compared the performance of these models. All three models demonstrated good predictive capabilities for SFTS cases, with the predicted results closely aligning with the actual cases. Among the models, the LSTM model exhibited the best fitting and prediction performance. It achieved the lowest values for mean absolute error (MAE), mean square error (MSE), and root mean square error (RMSE). The number of SFTS cases in the subsequent 5 years in this area were also generated using this model. The LSTM model, being simple and practical, provides valuable information and data for assessing the potential risk of SFTS in advance. This information is crucial for the development of early warning systems and the formulation of effective prevention and control measures for SFTS.

The imbalance of circulating monocyte subgroups with a higher proportion of the CD14+CD16+CD163+ phenotype in patients with preeclampsia.

BACKGROUND: Preeclampsia is a major cause of increased maternal and fetal morbidity and mortality, which is closely related to the abnormal maternal immune response. The skew of decidual macrophage polarization toward M1 phenotype has been proved to promote the pathogenesis of preeclampsia. However, it's not easy to monitor the change of decidual macrophage subtypes. The current study aims to examine the distribution of different circulating monocyte subtypes and analyze whether certain monocyte subtypes act as potential clinical indicators for preeclampsia. METHODS: A total of 50 pregnant women [mild preeclampsia (n = 20); severe preeclampsia (n = 15); healthy pregnancy (n = 15)] and 15 healthy donors were included in the study. Medical information such as BMI, blood pressure, ALT, creatinine, thrombocyte, etc., were recorded. The frequency of different monocyte subtypes in venous blood were measured by flow cytometry. Serum level of IL-6 was detected using Roche-Hitachi cobas 8000. Serum concentration of inflammatory cytokines (IL-1ß, IL-4, IL-10 and TNF-α) were measured by ELISA. RESULTS: A circulating monocyte subset with both M1 and M2 markers (CD14+CD16+CD163+) was found to occupy an obvious higher proportion in the preeclampsia group than in the normal pregnancy group. The ratio of CD206+/CD206- M2-like monocytes was also increased in the preeclampsia group, and meanwhile, it had statistic difference between the mild- and the severe-preeclampsia group. Furthermore, the serum levels of IL-1ß and TNF-α were positively correlated with the frequency of CD14+CD16+CD163+ intermediate monocytes in the preeclampsia group. CONCLUSIONS: The increased proportion of CD14+C16+CD163+ circulating monocytes and the high ratio of CD206+/CD206- M2-like monocytes may act as potential clinical indicators for preeclampsia, with the superiority of convenience and dynamic monitoring.

A potential tool for predicting epidemic trends and outbreaks of scrub typhus based on Internet search big data analysis in Yunnan Province, China.

Introduction: Scrub typhus, caused by Orientia tsutsugamushi, is a neglected tropical disease. The southern part of China is considered an important epidemic and conserved area of scrub typhus. Although a surveillance system has been established, the surveillance of scrub typhus is typically delayed or incomplete and cannot predict trends in morbidity. Internet search data intuitively expose the public's attention to certain diseases when used in the public health area, thus reflecting the prevalence of the diseases. Methods: In this study, based on the Internet search big data and historical scrub typhus incidence data in Yunnan Province of China, the autoregressive integrated moving average (ARIMA) model and ARIMA with external variables (ARIMAX) model were constructed and compared to predict the scrub typhus incidence. Results: The results showed that the ARIMAX model produced a better outcome than the ARIMA model evaluated by various indexes and comparisons with the actual data. Conclusions: The study demonstrates that Internet search big data can enhance the traditional surveillance system in monitoring and predicting the prevalence of scrub typhus and provides a potential tool for monitoring epidemic trends of scrub typhus and early warning of its outbreaks.

High prevalence of Rickettsia spp. in ticks from wild hedgehogs rather than domestic bovine in Jiangsu province, Eastern China.

Background: Spotted fever group Rickettsia (SFGR), containing various pathogenic Rickettsia spp., poses remarkable negative influences to public health by causing various severe or mild diseases. Information regarding prevalence of SFGR in ticks in Jiangsu province, Eastern China, is still limited and needs urgent investigations. Methods: Hedgehog- and bovine-attached ticks were collected from Jiangsu province, Eastern China. DNA of individual ticks was extracted for nested polymerase chain reaction amplifications targeting gltA, 16S ribosomal RNA (rrs), ompA, ompB, and sca4 genes following with sequencing. SFGR-specific IgG antibodies in sera of local donators were evaluated using ELISA. Results: Overall, 144 (83.2%) of the 173 ticks from hedgehogs and 2 (1.2%) of the 168 ticks from bovine were positive for one of the three identified Rickettsia spp., with significant difference between the two groups (P = 3.6e-52). Candidatus Rickettsia principis (9; 5.2%) and R. heilongjiangensis (135; 78.0%) were detected in Haemaphysalis flava rather than in H. longicornis ticks from hedgehogs. R. heilongjiangensis (1; 0.6%) and Candidatus R. jingxinensis (or Candidatus R. longicornii) (1; 0.6%) were identified in H. longicornis and Rhipicephalus microplus ticks from bovine, respectively. Phylogenetic analysis indicated Candidatus R. jingxinensis belonged to R. japonica subgroup, whereas Candidatus R. principis belonged to a novel subgroup. Higher serological prevalence of spotted fever and SFGR-specific IgG antibody level in humans were observed around the investigated area than in urban areas, without significant difference. Conclusion: Candidatus R. principis and Candidatus R. jingxinensis were identified in Jiangsu province, Eastern China, and fully genetically characterized for the first time. The higher prevalence of SFGR in hedgehog-attached ticks as well as the higher SFGR-specific IgG antibody level and seropositive rate in humans around the investigated area suggested that more attention should be paid to SFGR. This pathogen is usually transmitted or harbored by wild animals and ticks. This study provides important epidemiological data for both physicians and public health officers in developing early prevention and control strategies against potential Rickettsia infections and in the preparation of suitable testing and treatment needs for rickettsiosis in the endemic areas.

Wild Hedgehogs and Their Parasitic Ticks Coinfected with Multiple Tick-Borne Pathogens in Jiangsu Province, Eastern China.

The increasing awareness of emerging tickborne pathogens (TBPs) has inspired much research. In the present study, the coinfections of TBPs both in ticks and their wild hedgehog hosts in Jiangsu province, Eastern China were determined by metagenome next-generation sequencing and nested PCR. As a result, Rickettsia japonica (81.1%), novel Rickettsia sp. SFGR-1 (5.1%), Anaplasma bovis (12%), A. platys (6.3%), novel Ehrlichia spp. Ehr-1 (16%) and Ehr-2 (0.6%), E. ewingii-like strain (0.6%), Coxiella burnetii (10.9%), and a novel Coxiella-like endosymbiont (CLE) strain (61.1%) were detected in Haemaphysalis flava ticks. A. bovis (43.8%), Ehrlichia sp. Ehr-1 (83.3%), and C. burnetii (80%) were detected in Erinaceus amurensis hedgehogs. Coinfection rates with various TBPs were 71.5% and 83.3% in ticks and hedgehogs, respectively, both with double-pathogen/endosymbiont coinfection rates over 50%. We found the following. (i) Er. amurensis hedgehogs seem to contribute to the natural cycles of R. japonica, A. bovis, Ehrlichia sp., and C. burnetii and may be reservoirs of them except for R. japonica, and A. bovis is proved to infect hedgehogs for the first time. (ii) H. flava is proved to harbor various TBPs as a reservoir host, including CLE identified for the first time, which could inhibit coinfection of C. burnetii while promoting that of Rickettsia spp. in H. flava. (iii) Four novel TBP species were identified. This study provides useful epidemiological information crucial for assessing the potential infection risks to humans, thus benefiting the development of strategies to prevent and control tick-borne diseases. IMPORTANCE In the present study, we found the following. (i) Er. amurensis hedgehogs seem to contribute to the natural cycles of R. japonica, A. bovis, Ehrlichia sp., and C. burnetii and may be reservoirs of them except for R. japonica, and A. bovis is proved to infect hedgehogs for the first time. (ii) H. flava is proved to harbor various tickborne pathogens (TBPs) as a reservoir host, including Coxiella-like endosymbiont (CLE) identified for the first time, which could inhibit coinfection of C. burnetii while promoting that of Rickettsia spp. in H. flava. (iii) Four novel TBP species were identified. This study provides useful epidemiological information on TBPs harbored and transmitted by ticks and their hosts, for assessing the potential infection risks to humans, thus benefiting the developing strategies for tick-borne diseases prevention and control.

Co-existence of Multiple Anaplasma Species and Variants in Ticks Feeding on Hedgehogs or Cattle Poses Potential Threats of Anaplasmosis to Humans and Livestock in Eastern China.

Background: Anaplasma spp., causative agents of anaplasmosis, pose significant a threat to public health and economic losses in livestock farming. Co-infections/co-existence of various Anaplasma spp. may facilitate pathogen interactions and the emergence of novel variants, represent potential dangers to public health and economic losses from livestock farming, and raise challenges of detection and diagnosis. The information regarding co-infection/co-existence of Anaplasma in their vector ticks and wild animals is limited and needs urgent investigation. Methods: Wild hedgehogs and ticks from hedgehogs and cattle were collected from Jiangsu province, Eastern China, and DNA was extracted from hedgehog organs and tick homogenates. Various genera of species-specific polymerase chain reaction (PCR) or nested PCR amplifications targeting 16S ribosomal RNA (rrs), msp4, or groEL gene coupled with sequencing were conducted to identify Anaplasma spp. Results: Anaplasma phagocytophilum (1, 0.6%), A. marginale (2, 1.2%), A. platys variants xyn10pt-1 (13, 7.7%), xyn21pt-2 (3, 1.8%), and xyn3pt-3 (3, 1.8%), A. bovis variant cwp72bo-1 (12, 7.1%), and a novel Candidatus Cryptoplasma sp. (1, 0.6%) were identified in 168 Haemaphysalis longicornis ticks from cattle. A. platys variant xyn10pt-1 (20, 11.4%) and A. bovis variants cwp72bo-1 (12, 6.9%) and cwp55-36bo-2 (1, 0.6%) were detected in 173 H. flava ticks from hedgehogs. However, only A. bovis variant cwp72bo-1 (15, 46.7%) was identified in 32 Erinaceus amurensis hedgehogs. Various co-existence combinations were found only in ticks. Conclusion: The co-existence of various Anaplasma spp. and variants in H. flava and H. longicornis was detected for the first time in the world. The high infection rate of A. bovis in hedgehogs and its moderate infection rate in their parasitic ticks suggest that Er. amurensis hedgehog could be an important reservoir of A. bovis, rather than A. platys. Horizontal transmission of Anaplasma spp. may exist among different tick species via their shared hosts in the investigated area. This study provided epidemiological data that could be crucial for strategy development for early warning, prevention, and control of potential Anaplasma infections.

A multi-epitopes tandem antigen for five types of human adenoviruses and its application in development of multivalent IgM immunochromatographic strip test.

In China, human adenovirus serotype 3 (HAdV-3), HAdV-7, HAdV-11, HAdV-14, and HAdV-55 are the main prevalent serotypes causing severe acute respiratory diseases and even deaths. To develop multivalent vaccine and diagnostic reagent, a multi-epitopes tandem antigen (META) was designed. Recombinant META was prepared and its humoral immunogenicity, inducing neutralization antibody ability, antigenicity, and reactogenicity were evaluated. A multivalent immunochromatographic strip constructed using the rMETA was evaluated for its sensitivity and specificity in detecting specific IgM antibodies. As a result, the rMETA induced high titers of specific IgG antibodies, with limited abilities of neutralizing multiple HAdVs. It performed both strong antigenicity and reactogenicity. The multivalent immunochromatographic strip recognized specific IgM antibodies against all the 5 types with sensitivities of 87.5% to 95.3%. It performed high specificity of 97.8%. The present study provides both novel idea for developing multivalent vaccine and reagent for point-of-care detection of multiple types of HAdVs.

Development of Rapid and Visual Nucleic Acid Detection Methods towards Four Serotypes of Human Adenovirus Species B Based on RPA-LF Test.

OBJECTIVES: Human adenoviruses (HAdV) are classified as 7 HAdV species, and some serotypes in species B like HAdV 3, HAdV 7, HAdV 21, and HAdV 55 caused severe symptoms, even fatalities. Patients may be misdiagnosed and inadequately treated without reliable and practical methods for HAdV serotyping. Developing rapid, sensitive, and specific diagnostic methods for HAdV is critical. METHODS: Detection methods were established based on a recombinase polymerase amplification (RPA) assay and lateral flow (LF) test. Specific target sequence was screened, targeting which, primers and probes were designed, synthesized, and screened for establishing assay with high amplification efficiency. Primer or probe concentrations and amplification time were optimized. Detection limit, sensitivity, and specificity were evaluated. Results and Conclusions. Simple, sensitive, and specific RPA-LF methods for detection of four serotypes of HAdV together or separately were established, which had detection limits of 10 to 280 copies/reaction comparable to real-time PCR without recognizing other pathogens. The sensitivity and specificity were >92% and >98%, respectively, evaluated by limited clinical samples. The detection can be completed in 25 min without requirement of any instrument except a constant temperature equipment, showing superior detection performance and promising for a wide use in the field and resource-limited area.

Toxoplasmosis complicating lung cancer: a case report.

Toxoplasmosis complicating lung cancer has been described only rarely. Here, we report a case of acute Toxoplasma gondii infection in a patient with squamous lung cancer. A 64-year-old woman was admitted to our hospital with a history of cough of 6 months' duration and chest pain of 1 week's duration. Further examination revealed multiple swollen lymph nodes, palpable on the top of the right collarbone and without tenderness. The chest X-ray, bronchoscopy, and computed tomography scan confirmed squamous carcinoma of the right lung. The Wright-stained bronchoalveolar-lavage fluid cytology diagnosis was positive for T. gondii and tachyzoites were detected. All of them were of free type (ectocytic), without intracellular parasites. Serological examination revealed that the anti-T. gondii immunoglobulin (Ig) M and IgG antibodies were positive. Unfortunately the patient did not continue treatment and was lost to follow-up. Toxoplasmosis is a life-threatening opportunistic infection in patients with lung cancer. Prompt recognition of T. gondii infection among cancer patients with subsequent targeted treatment of toxoplasmosis could help alleviate symptoms and improve survival.

A concise synthesis of 3-(1-alkenyl)isoindolin-1-ones and 5-(1-alkenyl)pyrrol-2-ones by the intermolecular coupling reactions of N-acyliminium ions with unactivated olefins.

A concise synthesis of 3-(1-alkenyl)isoindolin-1-ones and 5-(1-alkenyl)pyrrol-2-ones has been achieved by the coupling reactions of N-acyliminium ions produced from 3-hydroxyisoindol-1-ones or 5-hydroxy-1-pyrrol-2-ones with unactivated olefins in the presence of BF(3)·OEt(2) at room temperature. For most of the olefins, the reactions afforded the C(sp3)-C(sp2) cross-coupling products, but for the α-methylstyrene and 1-hexene, the C(sp3)-C(sp3) cross-coupling products were obtained.